This is an equipment supplement application for a Program Project Grant (P01AG066606, June 1, 2021-February 28, 2026, PI: Zheng, Hui). The overarching goal of the parent P01 is to investigate the lysosome-to-nucleus signaling pathways regulating lysosomal homoeostasis in aging and Alzheimer’s disease. The P01 consists of three highly interactive projects and two scientific cores, which are overseen by an administration and data integration core. One of the essential components of the P01 is Core C: Lysosomal Metabolomics and pH. The Core uses high-throughput Mass Spectrometer-based metabolomics to assess changes in lysosomal metabolic activity in aging and tauopathy. The Core C Leader, Meng Wang, is a Professor at Baylor College of Medicine and an Investigator of the Howard Hughes Medical Institute (HHMI). She owns a Thermo Orbitrap Fusion Lumos Tribrid Mass Spectrometer for the lysosomal metabolomics experiments. Recently Dr. Wang has decided to leave Baylor and take on a new position at HHMI Janelia Research Campus, effective August 1, 2022. The Janelia organization is exclusively supported by HHMI and, as a result, Dr. Wang is no longer able to participate in the PPG. In addition, since Dr. Wang purchased mass spec using the HHMI funds, she will need to take the instrument to her new post. We have identified Dr. Feng Li, Associate Professor in the Center for Drug Discovery and the Department of Pathology & Immunology at Baylor College of Medicine and an expert in LC-MS metabolomics, to replace Dr. Wang as the leader for Core C. We have discussed this change and the need for a mass spec with Dr. Paul Barrett, the PO of the P01, who is supportive of the equipment supplement application to purchase a Thermo Scientific™ Orbitrap Exploris 120 LC/MS system to perform lysosome-specific metabolomic profiling as proposed in the parent P01.